DCT
1:17-cv-01606
Biogen Intl GmbH v. Sandoz Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Biogen International GmbH (Switzerland) and Biogen MA Inc. (Massachusetts)
- Defendant: Sandoz Inc. (Colorado)
- Plaintiff’s Counsel: Davis Graham & Stubbs LLP
- Case Identification: 1:17-cv-01606, D. Colo., 06/30/2017
- Venue Allegations: Plaintiff alleges venue is proper in the District of Colorado because Defendant [Sandoz Inc.](https://ai-lab.exparte.com/party/sandoz-inc) is a Colorado corporation. Plaintiff notes that it believes the case belongs in Delaware but filed in Colorado out of an abundance of caution.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff’s Tecfidera® product constitutes infringement of three patents covering pharmaceutical formulations and methods for treating multiple sclerosis.
- Technical Context: The technology concerns oral pharmaceutical formulations of dimethyl fumarate for the treatment of autoimmune diseases, particularly relapsing forms of multiple sclerosis.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 210414 and issuance of a notice letter to Plaintiff on June 9, 2017. The asserted patents are listed in the FDA's Orange Book for Plaintiff's branded drug, Tecfidera®. U.S. Patent No. 8,399,514 previously survived an inter partes review proceeding (IPR2015-01993), in which all challenged claims were found patentable. U.S. Patent Nos. 6,509,376 and 7,320,999 are subject to terminal disclaimers.
Case Timeline
| Date | Event |
|---|---|
| 1998-11-19 | Priority Date for U.S. 6,509,376 Patent |
| 1998-11-19 | Priority Date for U.S. 7,320,999 Patent |
| 2003-01-21 | Issue Date for U.S. 6,509,376 Patent |
| 2007-02-08 | Priority Date for U.S. 8,399,514 Patent |
| 2008-01-22 | Issue Date for U.S. 7,320,999 Patent |
| 2013-03-19 | Issue Date for U.S. 8,399,514 Patent |
| 2013-03-27 | FDA Approval of Tecfidera® (NDA No. 204063) |
| 2017-06-09 | Biogen receives Notice Letter from Sandoz |
| 2017-06-30 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,509,376 - "Utilization of Dialkyfumarates," Issued Jan. 21, 2003
The Invention Explained
- Problem Addressed: The patent describes the significant side effects associated with existing immunosuppressive agents used to treat autoimmune diseases and prevent graft rejection in transplant patients, including weakened immunity and an increased risk of malignant diseases (’376 Patent, col. 2:56-64).
- The Patented Solution: The invention is a pharmaceutical preparation containing dialkyl fumarates formulated into micro-tablets or micro-pellets, optionally with an enteric coating (’376 Patent, col. 3:5-13, 36-38). This formulation is designed to improve tolerance and reduce gastrointestinal side effects by releasing the active ingredient in smaller dosages distributed throughout the intestine, thereby avoiding the high local concentrations that can cause irritation (’376 Patent, col. 5:29-55).
- Technical Importance: The technology offered a potential improvement in the tolerability of fumaric acid-based therapies, which were known to have therapeutic potential but were hampered by side effects, particularly in the gastrointestinal tract (’376 Patent, col. 5:30-41).
Key Claims at a Glance
- The complaint asserts at least claim 1 (Compl. ¶24).
- Independent Claim 1 requires:
- A pharmaceutical preparation in the form of microtablets or micropellets.
- The preparation comprises one or more dialkyl fumarates of a specified chemical formula.
- The preparation is for use in transplantation medicine or for the therapy of specified autoimmune diseases, including multiple sclerosis.
- The complaint’s allegation of infringement of "at least one claim including at least claim 1" implicitly reserves the right to assert other claims, including dependent claims (Compl. ¶24).
U.S. Patent No. 7,320,999 - "Dimethyl Fumarate for the Treatment of Multiple Sclerosis," Issued Jan. 22, 2008
The Invention Explained
- Problem Addressed: The patent, which shares a specification with the ’376 patent, addresses the need for effective treatments for autoimmune diseases like multiple sclerosis while avoiding the drawbacks of conventional immunosuppressants (’999 Patent, col. 2:54-63).
- The Patented Solution: The invention is a method of treating multiple sclerosis by administering a pharmaceutical preparation where dimethyl fumarate is the sole active ingredient (’999 Patent, col. 8:14-20). By claiming a specific method of use with a single active agent, the patent carves out a distinct therapeutic regimen from the broader composition claims of its parent.
- Technical Importance: The patent claims a specific method of using only dimethyl fumarate to treat multiple sclerosis, providing a targeted therapeutic approach for this specific neurological disease (’999 Patent, col. 8:14-15).
Key Claims at a Glance
- The complaint asserts at least claim 1 (Compl. ¶38).
- Independent Claim 1 requires:
- A method of treating multiple sclerosis.
- The method comprises treating a patient with an effective amount of a pharmaceutical preparation.
- The only active ingredient for the treatment of multiple sclerosis present in said pharmaceutical preparation is dimethyl fumarate.
- The complaint’s broad infringement allegation implicitly reserves the right to assert dependent claims (Compl. ¶38).
U.S. Patent No. 8,399,514 - "Treatment for Multiple Sclerosis," Issued Mar. 19, 2013
Technology Synopsis
This patent describes a method for treating neurological diseases, such as multiple sclerosis, by administering a compound that provides neuroprotection. The technology is based on the discovery that certain compounds, including dimethyl fumarate, upregulate the Nrf2 cellular pathway, which protects against oxidative stress and is implicated in the pathogenesis of neurodegenerative diseases (’514 Patent, col. 1:12-20, col. 2:15-24). The invention claims a specific dosage regimen for treating MS.
Asserted Claims
The complaint asserts at least claim 1 (Compl. ¶53). Independent claim 1 is a method of treating multiple sclerosis by orally administering a pharmaceutical composition consisting essentially of a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination, wherein the effective amount is about 480 mg per day (’514 Patent, col. 28:57-65).
Accused Features
The accused feature is the use of Sandoz's generic product according to its anticipated label, which is expected to instruct for a dosage regimen that meets the "about 480 mg per day" limitation for the treatment of multiple sclerosis (Compl. ¶¶ 53, 56).
III. The Accused Instrumentality
- Product Identification: The accused instrumentalities are Sandoz's "generic dimethyl fumarate delayed-release capsules containing 120 mg and 240 mg of dimethyl fumarate" for which Sandoz seeks FDA approval via ANDA No. 210414 (Compl. ¶¶ 6, 21).
- Functionality and Market Context: The product is a generic version of Biogen's Tecfidera®, an oral drug approved for the treatment of relapsing forms of multiple sclerosis (Compl. ¶¶ 6, 19-20). The act of infringement alleged in an ANDA case is the submission of the ANDA itself, which seeks approval to market the generic drug for the same FDA-approved use as the branded product before the expiration of the patents-in-suit (Compl. ¶¶ 25, 39, 54). The complaint alleges that upon approval, Sandoz’s product label will instruct physicians and patients to use the drug in an infringing manner (Compl. ¶¶ 41-42, 56).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
6,509,376 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| Pharmaceutical preparation in the form of microtablets or micropellets... | Defendant's generic product is a delayed-release capsule alleged to be a generic equivalent of Tecfidera®, which is formulated with microtablets. | ¶¶ 21, 25 | col. 4:11-13 |
| ...comprising one or more dialkyl fumarates... | Defendant's generic product contains dimethyl fumarate as its active ingredient in 120 mg and 240 mg strengths. | ¶21 | col. 3:25-27 |
| ...for use in...therapy of autoimmune diseases such as...multiple sclerosis... | Defendant's ANDA seeks approval to market its generic product for the treatment of relapsing forms of multiple sclerosis. | ¶¶ 6, 21 | col. 8:23-24 |
7,320,999 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating multiple sclerosis comprising treating a patient...with an amount of a pharmaceutical preparation effective for treating said multiple sclerosis, | The proposed product label for Defendant's generic will instruct physicians and patients to administer the drug for the treatment of multiple sclerosis. | ¶¶ 40-42 | col. 8:14-18 |
| ...wherein the only active ingredient for the treatment of multiple sclerosis present in said pharmaceutical preparation is dimethyl fumarate. | Defendant's ANDA product is a pharmaceutical preparation that contains dimethyl fumarate as its only active ingredient. | ¶¶ 21, 42 | col. 8:18-20 |
- Identified Points of Contention:
- Scope Questions: A primary question for the ’376 patent is one of scope: does the formulation within Sandoz’s capsules meet the definition of "microtablets or micropellets"? The litigation will likely involve detailed analysis of the physical characteristics of Sandoz’s proposed generic product to determine if it falls within the scope of this limitation.
- Technical Questions: For the ’999 and ’514 method patents, the infringement analysis centers on the instructions for use. A key question will be whether the content of Sandoz’s proposed product label, which must copy the label of the branded drug, will necessarily direct or encourage physicians and patients to perform the patented methods, including the specific dosage regimen of "about 480 mg per day" required by the ’514 patent.
V. Key Claim Terms for Construction
The Term: "microtablets or micropellets" (’376 Patent, Claim 1)
- Context and Importance: This structural limitation is central to the infringement analysis for the ’376 patent. The case may turn on whether Sandoz’s formulation, contained within its delayed-release capsules, constitutes "microtablets or micropellets" or an alternative formulation (e.g., granules, coated particles) that falls outside the claim’s scope.
- Intrinsic Evidence for a Broader Interpretation: The specification suggests these terms encompass a range of small, solid forms, stating that the mean diameter can be in the range of 300 to 2,000 µm (’376 Patent, col. 3:50-53). This could support a reading that includes various small, compacted particulate forms.
- Intrinsic Evidence for a Narrower Interpretation: The patent’s examples describe specific processes for making "convex tablets" via compression and "pellets" by coating nonpareil seeds (’376 Patent, Examples 1, 2, 3). A party could argue these examples limit the term to forms created by conventional tabletting or pelleting techniques, potentially excluding other types of granulated or extruded drug particles.
The Term: "about 480 mg per day" (’514 Patent, Claim 1)
- Context and Importance: This dosage limitation is critical for infringement of the ’514 patent. Practitioners may focus on this term because the dispute will likely concern whether the instructions on Sandoz's label direct a daily dosage that falls within a reasonable interpretation of "about" 480 mg.
- Intrinsic Evidence for a Broader Interpretation: The term "about" is generally understood to afford some flexibility around the stated number. A party advocating for a broader scope would argue it covers dosages that are functionally equivalent or close to 480 mg, such as a standard dosing regimen that achieves this total daily amount (e.g., 240 mg twice daily).
- Intrinsic Evidence for a Narrower Interpretation: The patent does not provide an explicit definition for the range covered by "about." A party arguing for a narrower scope could contend that the term must be limited to the specific dosages tested and described, and that Sandoz's labeled dosage, if it deviates, falls outside this scope. The claims themselves, however, consistently use this "about 480 mg" language, suggesting it is a deliberately chosen and central feature of the invention (’514 Patent, claims 1, 11, 15, 20).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Sandoz will induce infringement of the ’999 and ’514 method patents. This is based on the allegation that Sandoz, by marketing a generic drug with a label copied from Tecfidera®, will actively encourage and instruct physicians and patients to administer the drug in a manner that directly infringes the patented methods (Compl. ¶¶ 41, 56). The complaint also alleges contributory infringement on the grounds that the generic product is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶¶ 42, 57).
- Willful Infringement: While the complaint does not use the word "willful," it alleges that Sandoz has "actual knowledge" of each asserted patent as a result of the ANDA process and the June 9, 2017 Notice Letter (Compl. ¶¶ 23, 37, 52). These allegations establish a basis for a potential future claim of willful infringement, particularly for any infringing acts that occur after Sandoz was on notice of the patents.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of structural form: will discovery show that Sandoz’s generic dimethyl fumarate formulation is embodied as "microtablets or micropellets," as required by the ’376 patent, or has Sandoz engineered a bioequivalent formulation with a different physical structure that may fall outside the claim’s scope?
- A key evidentiary question will be one of labeled instruction: does the FDA-approved label that Sandoz must adopt for its generic product direct a treatment method that meets all limitations of the asserted method claims, particularly the specific dosage of "about 480 mg per day" recited in the ’514 patent?
- The case may also raise questions of patent validity and scope, especially given the patents' prosecution histories. While the ’514 patent’s survival of an IPR challenge strengthens its position, Sandoz may still challenge validity on other grounds or contest the scope of the claims in view of the terminal disclaimers filed for the ’376 and ’999 patents.